Chemical Synthesis of an Erythropoietin Glycoform Containing a Complex‐type Disialyloligosaccharide

Murakami, Masumi; Okamoto, Ryo; Izumi, Masayuki; Kajihara, Yasuhiro

doi:10.1002/anie.201109034

Cited by 141 publications

(92 citation statements)

References 69 publications

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“…A hydrolysis reaction using 40 mM HCl indeed hydrolyzed the non-protected sialoside 19 (Figure 4), but did not affect the sialoside 28 protected with the phenacyl group. These results indicate that the carboxylic acid of sialoside acts as an intramolecular acid catalyst to accelerate acid hydrolysis, 32 rather than the electron donation by the 3-deoxyl structure.…”

Section: Synthesis Of Glycopeptide and Their Thioester Formmentioning

confidence: 92%

“…Our research group employed the in situ neutralization conditions established by the Kent and Alewood groups 30,33 while examining deprotection with tri- fluoromethane sulfonic acid (TfOH) in TFA. 32 The linker was selected in order to use a simple mercaptopropionic acid in which the carboxylic acid and thiol were designed so as to link with amino-resins and to form a thioester with the C-terminal amino acid, respectively ( Figure 6B). Therefore, since the peptide linked with the resin through a thioester linker was not cleaved by TfOH/TFA, we can examine the deprotection of the side-chain protecting groups repeatedly until all of the protecting groups are removed.…”

Section: Synthesis Of Glycopeptide and Their Thioester Formmentioning

confidence: 99%

“…After purification, the correctly folded glycosyl-EPO 60 was characterized by ESImass spectrometry ( Figure 11E), CD spectrometry and disulfide bond mapping. 47 Because the homogeneous EPO derivatives were obtained by chemical synthesis and semisynthesis, bioassays for cell proliferation were examined using both in vitro and in vivo conditions (Figure 12). In the in vitro experiments, the synthesized EPO exhibited suitable cell proliferation activity, but very weak or no activity was observed in in vivo experiments.…”

Section: ¼ 14)mentioning

confidence: 99%

“…47 Our chemical synthetic strategy employed 6 segment-coupling by NCL ( Figure 11A). However, EPO does not have an adequate number of cysteines for the repetitive NCL reactions required to have a whole polypeptide.…”

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confidence: 99%

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Studies on the Precise Chemical Synthesis of Human Glycoproteins

Kajihara¹

2015

Bulletin of the Chemical Society of Japan

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Our research group demonstrated the semi-synthesis of complex-type biantennary sialyloligosaccharide-library by means of branch-specific glycosidase and several sialyltransferase reactions toward complex-type H 2 N-Asn-(biantennary compex-type sialyloligosaccharide)-COOH isolated from egg yolk at over a gram scale. This methodology yielded 35 kinds of homogeneous complex-type oligosaccharides. Using this oligosaccharide library, an efficient Boc solid phase peptide synthesis (SPPS) of acid labile sialylglycopeptide-α-thioester was demonstrated. Our research group showed that the sialoside in which the carboxylic acid is protected with a phenacyl group is stable under strong acidic conditions, and this critical finding enabled us to demonstrate the first Boc-SPPS for the synthesis of a sialylglycopeptide-α-thioester. Using both a synthetic method of sialylglycopeptide-α-thioester and native chemical ligation (NCL), our research group synthesized several glycoproteins such as chemokine MCP-3, three kinds of erythropoietin analogues, and interferon-ß. Our research group also demonstrated a unique synthesis that was an intentional synthesis of homogeneous misfolded glycoproteins bearing M9-high-mannose-type oligosaccharide. This unique synthetic misfolded-glycoprotein is useful for the purpose of uncovering the mechanism of molecular recognition in glycoprotein quality control (GQC) in the endoplasmic reticulum (ER). This account discusses the function of the oligosaccharides of glycoproteins based on our research findings.

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Section: Synthesis Of Glycopeptide and Their Thioester Formmentioning

confidence: 92%

Section: Synthesis Of Glycopeptide and Their Thioester Formmentioning

confidence: 99%

Section: ¼ 14)mentioning

confidence: 99%

mentioning

confidence: 99%

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Studies on the Precise Chemical Synthesis of Human Glycoproteins

Kajihara¹

2015

Bulletin of the Chemical Society of Japan

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“…To obtain homogeneous glycoproteins, chemical synthesis has become an alternative method because of its dramatic advance in recent years (34)(35)(36)(37). Therefore, we examined the first chemical Fig.…”

Section: Chemical Approachesmentioning

confidence: 99%

Misfolded Glycoproteins as Probes for Analysis of Folding Sensor Enzyme UDP-Glucose

Izumi

Kiuchi

Ito

et al. 2013

TIGG

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Amide‐Forming Ligation Reactions

2019

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One of the long‐standing pursuits of synthetic organic chemists is the development of chemical methods for the synthesis of peptides and proteins as tools for understanding biological processes and providing therapeutic solutions to human diseases. The advent of chemoselective ligation reactions for the chemical synthesis of peptides and proteins has enabled synthetic chemists to realize this long‐held dream. In an amide‐forming ligation reaction, two uniquely placed functional groups within the peptide allow peptide or protein segments to be joined in a chemoselective manner with an amide bond. In this chapter, some of the early methods based on principles of the capture/rearrangement strategy for ligation of peptides are catalogued, followed by some of the most versatile and well‐established contemporary methods for the preparation of linear/cyclic peptides and proteins such as the native chemical ligation (NCL) and the α‐ketoacid–hydroxylamine (KAHA) ligation. The chapter concludes with some of the most promising new generation ligation methods such as the potassium acyltrifluoroborate–hydroxylamine (KAT) ligation. The tremendous progress in the past two decades in the development of several ligation methods that rely on a pair of unique functional groups is set to expand the horizons of fully functional proteins and multi‐protein assemblies that are purely synthetically prepared. Although contemporary ligation reactions do not match the speed and efficiency at which proteins are assembled in biological systems, the repertoire of chemoselective amide‐forming ligation methods has already enabled synthetic protein chemistry to surpass biology in terms of chemical and structural diversity.

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Chemical Synthesis of an Erythropoietin Glycoform Containing a Complex‐type Disialyloligosaccharide

Cited by 141 publications

References 69 publications

Studies on the Precise Chemical Synthesis of Human Glycoproteins

Studies on the Precise Chemical Synthesis of Human Glycoproteins

Misfolded Glycoproteins as Probes for Analysis of Folding Sensor Enzyme UDP-Glucose

Amide‐Forming Ligation Reactions

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